Abstract
Experimental allergic encephalomyelitis (EAE) serves as a model for autoimmune diseases mediated by T lymphocytes1,2. Following sensitization to rat, mouse or guinea pig myelin basic protein (MBP) in complete Freund's adjuvant, inbred mouse strains PL/J (H–2u, SJL/J (H–2s) and (PL/J × SJL/J)F1((PLSJ)F1) develop EAE3,4. Whereas sensitization to the N-terminal 37 amino-acid peptide of rat or guinea pig MBP [MBP(1–37)] induces EAE in PL/J mice, immunization to the C-terminal peptide (89–169) leads to EAE in SJL/J mice4,5. The immune response to MBP in (PLSJ)F1 mice is not co-dominant; sensitization to the N-terminal peptide induces EAE, while sensitization to the C-terminal peptide does not3,4. We have generated MBP-specific T-cell clones restricted to class II (Ia) antigens of the major histocompatibility complex (MHC) from PL/J and (PLSJ)F1 mice following sensitization to rat MBP. Two such I–Au-restricted T-cell clones that proliferate in response to the encephalitogenic N-terminal MBP peptide and recognize a shared determinant with mouse (self) MBP cause paralysis in 100% of (PLSJ)F1 mice tested. Paralysis is induced even when recipients are injected with as few as 1 × 105 cloned T cells. Relapsing paralysis followed in two-thirds of the recipients after recovery from acute paralysis, whereas one-third developed chronic persistent paralysis, a form of EAE not usually seen. Histopathology revealed intense perivascular inflammation, demyelination and remyelination within the central nervous system of paralysed mice. The experimental disease induced with these clones shares important features with human demyelinating diseases such as multiple sclerosis. This is the first demonstration that T-cell clones that respond to a defined self-antigen can induce clinical and histological autoimmune disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ortiz-Ortiz, L. & Weigle, W. O. J. exp. Med. 144, 604–616 (1976).
Gonatas, N. K. & Howard, J. C. Science 18, 839–841 (1974).
Fritz, R. B., Jen Chou, C. H. & McFarlin, D. E. J. Immun. 130, 191–194 (1983).
Jen Chou, C. H., Shapira, R. & Fritz, R. B. Prog. clin. Biol. Res. 146, 229–234 (1984).
Pettinelli, C. B., Fritz, R. B., Jen Chou, C. H. & McFarlin, D. E. J. Immun. 126, 1209–1214 (1982).
Pettinelli, C. B. & McFarlin, D. E. J. Immun. 127, 1420–1423 (1981).
Mokhtarian, F., McFarlin, D. & Raine, C. S. Nature 309, 356–358 (1984).
Ben Nun, A. & Lando, Z. J. Immun. 130, 1205–1209 (1983).
Trotter, J. et al. J. Immun. 134, 2322–2327 (1985).
Ben Nun, A., Wekerle, H. & Cohen, I. R. Nature 293, 60–61 (1981).
Martenson, R. E. Prog. clin. Biol. Res. 146, 511–521 (1984).
Frelinger, J. G. et al. J. exp. Med. 59, 704–715 (1984).
Beck, B. N. et al. J. exp. Med. 156, 1186–1194 (1982).
Lando, Z. & Ben Nun, A. Clin. Immun. Immunopath. 30, 290–295 (1984).
Steinman, L., Rosenbaum, J. T., Sriram, S. & McDevitt, H. O. Proc. natn. Acad. Sci. U.S.A. 78, 7111–7114 (1981).
Sriram, S. & Steinman, L. J. exp. Med. 158, 1362–1367 (1983).
Waldor, M. et al. Science 227, 415–417 (1985).
Brostoff, S. W. & Mason, D. J. Immun. 133, 1938–1942 (1984).
Wong, G. H. W., Bartlett, P. F., Clark-Lewis, I., Battye, F. & Schrader, J. R. Nature 310, 688–691 (1984).
Fontana, A., Fierz, W. & Wekerle, H. Nature 307, 273–276 (1984).
Traugott, U., Raine, C. S. & McFarlin, D. E. Cell. Immun. 91, 240–254 (1985).
Trotter, J. & Steinman, L. J. Immun. 132, 2919–2923 (1983).
Kimoto, M. & Fathman, C. G. J. exp. Med. 152, 759–770 (1980).
Smith, M. E. Neurochemistry 16, 83–92 (1969).
Oi, V. T., Jones, P. P., Goding, J. W., Herzenberg, L. A. & Herzenberg, L. A. Clin. Topics Microbiol. Immun. 81, 115–129 (1978).
Pierres, M. C., Devaux, M. D. & Marchett, S. Immunogenetics 14, 481–495 (1981).
Ozato, K., Mayer, N. & Sachs, D. H. J. Immun. 124, 533–540 (1980).
Lerner, E. A. et al. J. exp. Med. 152, 1085–1101 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zamvil, S., Nelson, P., Trotter, J. et al. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317, 355–358 (1985). https://doi.org/10.1038/317355a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/317355a0
This article is cited by
-
B cell depletion therapies in autoimmune disease: advances and mechanistic insights
Nature Reviews Drug Discovery (2021)
-
Unwanted help from T cells in the aging central nervous system
Nature Aging (2021)
-
Inducing immune tolerance with dendritic cell-targeting nanomedicines
Nature Nanotechnology (2021)
-
An emerging potential of metabolomics in multiple sclerosis: a comprehensive overview
Cellular and Molecular Life Sciences (2021)
-
Opposing T cell responses in experimental autoimmune encephalomyelitis
Nature (2019)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.